Phase 2
N=1,267
A Phase 2b Study of CSL112 in Subjects With Acute Myocardial Infarction.
Acute Myocardial Infarction
Bottom Line
View on ClinicalTrials.gov: NCT02108262 ↗Enrolled (actual)
1,267
Serious AEs
14.1%
Results posted
Mar 2021
Primary outcome: Primary: Percent of Participants With Clinically Important Change in Drug-induced Liver Injury — 1.0; 0.5; 0 percentage of participants — p== 0.1241
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- CSL112 (Biological); Placebo (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- CSL Behring
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent of Participants With Clinically Important Change in Drug-induced Liver Injury |
1.0; 0.5; 0 | = 0.1241 |
| PRIMARY Percent of Participants With Clinically Important Change in Renal Status |
0; 0.7; 0.2 | = 0.4988 |
| SECONDARY The Percentage of Participants With a Time-to-first Major Adverse Cardiovascular Event (MACE) |
6.4; 5.7; 5.5 | = 0.5733 |
| SECONDARY Change From Baseline in Concentrations of Apolipoprotein A-I (apoA-I) and Phosphatidylcholine (PC) at End of First Infusion for All Participants |
35.9; 136.1; -4.7; 57.7; 180.4; -1.2 | — |
| SECONDARY Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for All Participants |
52.1; 158.0; 5.4; 48.7; 186.8; -12.9 | — |
| SECONDARY Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Normal Renal Function |
36.0; 134.5; -4.0; 58.0; 177.4; -1.3 | — |
| SECONDARY Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Normal Renal Function |
54.7; 154.3; 4.8; 47.6; 182.0; -12.3 | — |
| SECONDARY Change From Baseline in Plasma Concentrations of apoA-I and PC at End of First Infusion for Participants With Mild Renal Impairment |
35.9; 135.5; -5.3; 57.8; 180.6; -0.8 | — |
| SECONDARY Change From Baseline in Plasma Concentrations of apoA-I and PC at End of Fourth Infusion for Participants With Mild Renal Impairment |
49.3; 158.4; 6.0; 50.6; 188.3; -13.2 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for All Participants |
42.6; 147.4; 7.1; 67.7; 196.4; 11.1 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for All Participants |
57.6; 164.3; 12.7; 59.0; 187.4; 9.1 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
40.9; 135.1; 7.8; 61.9; 184.9; 13.0 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
60.8; 149.0; 17.5; 45.8; 176.1; 20.1 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
44.6; 160.7; 5.2; 74.6; 211.3; 6.0 | — |
| SECONDARY Change From Baseline in Plasma Cmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
53.7; 169.7; 1.0; 74.8; 190.4; -17.4 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for All Participants |
2.23; 2.17; 46.8; 2.23; 2.17; 5.29 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for All Participants |
2.13; 2.25; 119; 2.17; 2.25; 46.93 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
2.25; 2.17; 96.1; 2.22; 2.17; 8.1 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
2.13; 2.17; 119.3; 2.17; 2.17; 29 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
2.18; 2.22; 0; 2.28; 2.22; 0 | — |
| SECONDARY Change From Baseline in Plasma Tmax for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
2.17; 2.25; 72.5; 2.17; 2.25; 48.3 | — |
| SECONDARY Change From Baseline in Plasma Area Under the Curve (AUC) AUC0 - Last for apoA-I and PC After First Infusion for All Participants |
1703; 4819; -766; -66.12; 869; -2096 | — |
| SECONDARY Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for All Participants |
4579; 8985; 747; 70.7; 2499; -2185 | — |
| SECONDARY Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
1278; 3762; -516; -1382; -137; -1337 | — |
| SECONDARY Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
4513; 8609; 1632; -2130; 3609; -542 | — |
| SECONDARY Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After First Infusion for Subjects With Mild Renal Impairment |
2205; 5917; -1416; 1489; 1828; -4068 | — |
| SECONDARY Change From Baseline in Plasma AUC0 - Last for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
4659; 8786; -1376; 2712; 1541; -6128 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for All Participants |
496; 1929; -168; 731; 2903; -331 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for All Participants |
881; 2392; -57; 1593; 3913; -55 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
418; 1653; -149; 547; 2521; -316 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
929; 2098; 20; 1668; 3459; 105 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
589; 2219; -218; 949; 3308; -370 | — |
| SECONDARY Change From Baseline in Plasma AUC0-t for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
823; 2469; -243; 1503; 4049; -440 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for All Participants |
1425; 6090; 1850; 1678; 6979 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for All Participants |
15540; 13570; 4615; 2015; 12863 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
589; 4505; 490; 1596 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
17079; 12422; 4615; 638; 16142 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
1842; 8032; 3210; 1761; 6979 | — |
| SECONDARY Change From Baseline in Plasma AUC0-∞ for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
11951; 13157; 4769; 12827 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for All Participants |
46.4; 53.9; 32.9; 9.7; 241.2 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for All Participants |
269.1; 103.6; 145; 21.5; 156.3 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
7.5; 41.4; 34; 12.3 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
271.6; 96.5; 145; 9.1; 121.1 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
65.9; 66.4; 31.8; 7.1; 241.2 | — |
| SECONDARY Change From Baseline in Plasma Terminal Half-life (t1/2) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
263.1; 99.2; 46.3; 185.6 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for All Participants |
0.29; 0.15; 0.32; 0.61 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for All Participants |
0.09; 0.07; 0.11; 0.57 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
0.33; 0.19; 0.41; 0.68 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
0.11; 0.08; 0.24; 0.19 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
0.27; 0.09; 0.26; 0.54 | — |
| SECONDARY Change From Baseline in Plasma Clearance (CL) for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
0.05; 0.08; 0.08; 1.01 | — |
| SECONDARY Change From Baseline in Plasma Volume of Distribution at Steady State (Vss) for apoA-I and PC After First Infusion for All Participants |
33.4; 7.4; 6.1; 14.4 | — |
| SECONDARY Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for All Participants |
18.7; 9.4; 10.7; 58.3 | — |
| SECONDARY Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Normal Renal Function |
3.8; 8.1; 8.3; 24.7 | — |
| SECONDARY Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Normal Renal Function |
18.7; 9.4; 11.4; 17 | — |
| SECONDARY Change From Baseline in Plasma Vss for apoA-I and PC After First Infusion for Participants With Mild Renal Impairment |
48.2; 6.4; 4.7; 4 | — |
| SECONDARY Change From Baseline in Plasma Vss for apoA-I and PC After Fourth Infusion for Participants With Mild Renal Impairment |
18.7; 9.4; 9.3; 83.1 | — |
| SECONDARY Percent of Participants With the Occurrence of Suspected Adverse Drug Reactions |
31.8; 28.4; 23.5 | — |
| SECONDARY Percent of Participants With Any Adverse Event (AE) |
50.6; 51.4; 49.6 | — |
| SECONDARY Percent of Participants Who Experience Bleeding Events |
9.2; 9.1; 12.3 | — |
| SECONDARY Change From Baseline in Serum Antibodies to CSL112 and apoA-I |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Positive Serology Results for IgG and IgM Antibodies to Parvovirus B19 |
40; 48; 44; 0; 0; 0 | — |
| SECONDARY Number of Participants With Parvovirus B19 DNA in Serum |
57; 60; 59; 1; 0; 1 | — |
Summary
This is a multicenter randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase 2b study to investigate the hepatic and renal safety and tolerability of multiple dose administration of two dose levels of CSL112 compared with placebo in subjects with acute myocardial infarction (AMI).
Eligibility Criteria
Inclusion Criteria
- Men or women, at least 18 years of age, with evidence of myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI), in the last week.
Exclusion Criteria
- Ongoing hemodynamic instability
- Evidence of hepatobiliary disease
- Evidence of chronic kidney disease (CKD) (Stage III, IV, or V), defined as moderate or severe renal impairment or if subject is receiving dialysis
- Evidence of unstable renal function
- History of acute kidney injury after previous exposure to an intravenous contrast agent.
- Known history of allergies, hypersensitivity or deficiencies to CSL112 or any of its components
- Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study
Data sourced from ClinicalTrials.gov (NCT02108262). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.